國家衛生研究院 NHRI:Item 3990099045/9637
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    題名: Functional mechanism of hypoxia-inducible factor 1 alpha-mediated Dicer down-regulation
    其他題名: Functional mechanism of hypoxia-inducible factor 1 α-mediated Dicer down-regulation
    作者: Lai, HH;Lyu, YJ;Li, JN;Su, JL;Chen, PS
    貢獻者: National Institute of Cancer Research
    摘要: MicroRNAs (miRNAs) are generated by a multiple steps process that post-transcriptionally regulate the expression of target genes. Dysregulation of miRNAs is linked to human diseases including the development of human cancer. Abrogation of cellular global miRNAs maturation has been proposed to promote tumorigenesis and cancer metastasis. Hypoxia stress is the major cause of dysregulation of miRNAs and promotes tumor angiogenesis, metastasis and tumorigenesis which is a pivotal factor to switch on the cellular oncogenic features during tumor progression. Although hypoxia stress regulates expression of a subset of miRNAs, the upstream regulators controlling miRNAs regulation under hypoxia remain unclear. This study demonstrates the molecular mechanism of post-translational regulation of Dicer under hypoxia. Our results show that knockdown of hypoxia inducible factor 1 alpha (HIF-1α) up-regulates Dicer expression in colorectal cancer (CRC) cells. Overexpression of HIF-1α enhances ubiquitination of Dicer and subsequently promotes it recognition by autophagic receptor for autophagy-lysosomal degradation. We also find that HIF-1α enhances cancer cell migration by regulating Dicer-regulated miRNAs. In conclusion, we demonstrated that HIF-1α down-regulated Dicer and abolishes miRNA biogenesis to enhance cancer cell migration. This study may provide a potential therapeutic direction that targets the dysregulated miRNAs in tumor hypoxia for patients with poor prognosis and metastatic CRC.
    日期: 2015-08
    關聯: Cancer Research. 2015 Aug;75:Abstract number 199.
    Link to: http://dx.doi.org/10.1158/1538-7445.am2015-199
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0008-5472&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000371578500189
    顯示於類別:[蘇振良] 會議論文/會議摘要

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